The enhanced disease resistance 1 (edr1) mutation of Arabidopsis confers re
sistance to powdery mildew disease caused by the fungus Erysiphe cichoracea
rum. Resistance mediated by the edr1 mutation is correlated with induction
of several defense responses, including host cell death. Double mutant anal
ysis revealed that all edr1-associated phenotypes are suppressed by mutatio
ns that block salicylic acid (SA) perception (nim 1) or reduce SA productio
n (pad4 and eds1). The NahG transgene, which lowers endogenous SA levels, a
lso suppressed edr1. In contrast, the ein2 mutation did not suppress edr1-m
ediated resistance and associated phenotypes, indicating that ethylene and
jasmonic acid-induced responses are not required for edr1 resistance. The E
DR1 gene was isolated by positional cloning and was found to encode a putat
ive MAP kinase kinase kinase similar to CTR1, a negative regulator of ethyl
ene responses in Arabidopsis, Taken together, these data suggest that EDR1
functions at the top of a MAP kinase cascade that negatively regulates SA-i
nducible defense responses. Putative orthologs of EDR1 are present in monoc
ots such as rice and barley, indicating that EDR1 may regulate defense resp
onses in a wide range of crop species.